Treatment of mood disturbance in bipolar disorder is undergoing a paradigm shift. Traditionally, drug therapy has been focussed on efficacy in acute mania or depression. Now psychiatrists are realising the need to evaluate drug treatments from other perspectives, Their full effects as acute and mood-stabilising agents, side effect profiles, effects on neurocognitive functioning, quality of life, and on psychosocial functioning, are also important when considering therapy.

Bipolar disorder, the condition where mood swings between varying degrees of mania, hypomania, mixed states, depression and major depressive disorder, is now the sixth leading cause of disability according to the World Health Organization (1). But although bipolar disorder is as common as diabetes, much of it still goes unrecognised and inadequately treated. Official estimates put prevalence at between 1 to 4 per cent of the population but some researchers believe the real figure is closer to 10 per cent if the whole spectrum of bipolar disorder is included (2).

To be diagnosed as bipolar I patients must have experienced at least one severe manic episode lasting a week, or a mix of manic and depressive symptoms. Bipolar II can be diagnosed following one major depression and evidence of prior hypomanic episodes (3).

Bipolar disorder typically develops in a patient’s late teens or early twenties. In nine out of ten cases it recurs periodically throughout a course of around 20 years with an average of nine severe episodes. The ratio of depressive to manic episodes is more than two to one in western Europe. Compared with mania, episodes of depression are also of much longer duration and are associated with a higher risk of suicide (4,5) Between episodes there may be periods of stability, with only normal mood variation or minor symptoms, but admission to hospital becomes more likely with each relapse (6).

Bipolar illness is complex and variable making diagnosis difficult. "But early diagnosis and good treatment are crucial because the condition impacts on so many aspects of a person’s life” emphasises Professor Allan Young, a prominent specialist in the field from University of British Columbia, Vancouver, Canada.

In severe cases of bipolar 1 illness, symptoms can be psychotic and include delusions and hallucinations. More usually, symptoms of mania and hypomania are less obvious - euphoria, impulsivity, recklessness, and a diminished need for sleep can be ascribed to youthful exuberance. At the depressive end of the spectrum, feelings of anxiety, irritability, hostility and depression can lead to violent or suicidal behaviour. Around one third of bipolar sufferers currently attempt suicide and about half of those succeed (7,8). “There are other disorders to which bipolar individuals become more susceptible and which impact on physical health and wellbeing such as anxiety,” Professor Young adds. “There's also a strong risk of alcohol or substance abuse. On average, an uncontrolled sufferer will die nine years earlier than the rest of the population and experience 12 fewer years of healthy life.”

Effects on intellect affect work

Bipolar disorder sufferers are often highly intelligent and creative individuals but inability to keep the disorder in check is associated with high rates of unemployment and poor work performance (9). Recent US research estimates that bipolar disorder costs the country over $14 billion dollars per year in lost productivity (10).

Bipolar disorder takes a heavy toll on cognitive functioning, Professor Young points out. Not just through effects on memory but through more subtle changes collectively described as impaired executive functioning (11). “This includes ability to plan, organise and prioritise tasks, to focus attention where needed, process information and access working memory” he explained. “It’s the sort of thing we all take for granted but can be terribly disabling for bipolar patients. This kind of dysfunction can make it impossible to hold down a job or be considered for promotion (9).” Employment problems are twice as high among bipolar patients as their healthy peers and, on average, time in employment is reduced by 14 years.” Cognitive problems can be exacerbated by some drug treatments, particularly those which cause extrapyramidal symptoms (EPS) (12). These can also lead to social isolation, he noted.

A breakdown of relationships is a common consequence of the illness. Bipolar patients are twice as likely to divorce compared to the general population (13). Symptoms also have repercussions on social functioning when relationships with colleagues and friends as well as partners are lost. Even parents and siblings can find behaviours impossible to tolerate; estrangement and isolation are common tragic consequences of poorly controlled bipolar disorder.

Need for “ whole person” treatment

Bipolar sufferers who are eventually properly diagnosed– a process than can take up to 10 years – often then find treatment unsatisfactory.

Treatment has traditionally proved problematical for many patients and has meant high rates of non-adherence, says psychiatrist Dr Heinz Grunze of Ludwig-Maximilians-University, Munich, Germany. Many patients have been expected to take up to four types of drugs daily, including several associated with adverse effects including weight gain, somnolence, sexual dysfunction and involuntary movements (12,14). Not surprisingly, compliance with this type of schedule is poor.

Misdiagnosis can also confound treatment effectiveness. Treatment directed primarily at controlling and preventing mania or substance abuse,can fail to tackle depressive symptoms. “On the other hand, bipolar sufferers misdiagnosed as having anxiety or unipolar depression and treated with antidepressant drugs alone, are at high risk of deteriorating", explains Professor Young. A recent survey of over 7,500 bipolar patients presented at the 2007 American Psychiatric Association meeting shows over half of bipolar patients treated between 2001 and 2004 received an antidepressant drug alone as their initial therapy (15). This was "despite a lack of compelling evidence of their efficacy or safety in bipolar depression” commented the investigators. By the time they had been diagnosed one year, polypharmacy dominated treatment, they added.

The mood-stabilising therapy and former mainstay of bipolar treatment, lithium, is highly effective at controlling mania and is used as a maintenance therapy between episodes, as is the anticonvulsant valproate, but these drugs are now considered much less effective in preventing and controlling depressive symptoms. Lithium carries a need for blood monitoring and is associated with side effects including cognitive impairment and tremor that lead to high discontinuation rates. (16)

“We need to look at patients in a wider sense than before,” suggests Professor Young. Traditionally, the focus of drug therapy has been solely on mania or depression with drugs monitored only on symptom-rating scales for those symptoms. Functional recovery – a return to pre-morbid level of functioning - has been relatively neglected and less well assessed. Now psychiatrists are realising the need to evaluate drug treatments from other perspectives, besides efficacy in mania or depression (17). The full effects of therapies, including their side effect profiles, how they affect neurocognitive functioning, quality of life, psychosocial functioning and chronic low-grade symptoms, are also important. “It is these kind of assessments that can better highlight when treatment is falling short of providing therapy for the patient as a whole,” he comments. Only when every domain of bipolar illness is addressed, do patients have the best chance of fully recovering ability to participate in normal life.

New approaches

Most psychiatrists acknowledge treatment has advanced considerably over the past decade. Effective new drugs for rapidly controlling mania are now available that can be used instead of, or to allow a reduction of, lithium, Professor Young explains: "Newer antipsychotics, can control mania quickly without so many of the unwelcome side effects associated with older drugs. (18,19).Older treatments frequently adversely affect cognition and can cause involuntary movements that are distressing and stigmatising.” (16,12)

“What gets you well, keeps you well”

“The notion that treatment of acute episodes is followed by maintenance therapy with a mood-stabiliser is undergoing a paradigm shift,” notes Dr Grunze. “The view now is that ‘what gets you well, keeps you well.’

The fewer drugs a patient needs to take, the greater is the likelihood they will adhere well to treatment. But supplementing therapy should not necessarily need additional medication anyway, argue patient groups. Talking therapies are also key, they believe, as is psycho-education. Teaching patients to understand the nature of bipolar disorder and the importance of seeking help early is recognised as a necessary part of management for every patient. Psycho-education programmes explain when and why medicines must be taken regularly, and teach coping strategies. By avoiding destabilising triggers such as stress, overwork, and too little sleep, patients can help prevent acute episodes of mania and depression (20, 21, 22).

The new approach to managing bipolar illness across all its dimensions – physical, cognitive, emotional and social - using effective, well-tolerated medications and psychosocial interventions, gives scope for optimism. New research and new thinking are helping to improve greatly, the prospects for bipolar patients in restoring their life chances.

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